This study is an investigation of the regulation of the pulmonary circulation by hypoxia, hypercapnea and other humoral and pharmacologic agents, such as histamine and serotonin in the normal situation and in disease states. It is designed to elucidate the mechanisms whereby these gaseous and humoral agents produce pulmonary hypertension, such as is observed in patients with chronic lung disease and cor pulmonale and to study the effect of absence of this mechanism in patients who may possibly have non-reactive pulmonary vasculature, such as those with hepatic cirrhosis or familial dysautonomia. The techniques involve animal and in vitro methods to assess both the role of the pulmonary perivascular mast cell as a chemoreceptor releasing vasoactive materials and the physiology and pharmacology of the alpha and beta adrenergic system, which may make the pulmonary circulation in contrast to the systemic one uniquely sensitive to these vasoactive substances. An analysis of the handling by the lung, in terms of uptake, metabolism and secretion, of major substances such as histamine and serotonin and their precursors not only define mechanisms of pulmonary hypertension, but will also delineate the role of the lung in humoral metabolism both in health and in lung disease states.